Skip to main content
Top
Published in: Current Treatment Options in Oncology 12/2023

13-12-2023 | NSCLC

Perioperative Immunotherapy in Non-Small Cell Lung Cancer

Authors: Jenny O’Brien, MD, PhD, J. Nicholas Bodor, MD, PhD

Published in: Current Treatment Options in Oncology | Issue 12/2023

Login to get access

Opinion statement

The standard of care in patients with early-stage non-small cell lung cancer (NSCLC) following surgical resection has been adjuvant chemotherapy for the last two decades, despite modest improvements in survival and high rates of disease recurrence. Numerous clinical trials have reported practice-changing findings demonstrating a benefit in disease-free survival (DFS) or event-free survival (EFS) with perioperative immunotherapy. This has led to several recent regulatory approvals supporting the use of adjuvant immunotherapy or neoadjuvant immuno-chemotherapy in NSCLC, and such therapies are now an integral component of care for early-stage disease. However, in select cases, such as in the presence of certain tumor oncogenes associated with immunotherapy resistance, the use of checkpoint inhibitors in the perioperative setting should generally be avoided. This speaks to the importance of integrating routine tissue-based molecular profiling, that evaluates for tumor oncogene mutations and PD-L1 expression, into our practice when caring for patients with early-stage NSCLC. While an overall survival (OS) advantage has yet to be firmly established from many of the recent studies evaluating perioperative immunotherapy, it is expected that an OS benefit and higher rates of cure will become evident as these data mature, especially among patients with greater levels of tumor PD-L1 expression.
Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.CrossRefPubMed
2.
go back to reference Cronin KA, Scott S, Firth AU, Sung H, Henley SJ, Sherman RL, et al. Annual report to the nation on the status of cancer, part 1: National cancer statistics. Cancer. 2022;128(24):4251–84.CrossRefPubMed Cronin KA, Scott S, Firth AU, Sung H, Henley SJ, Sherman RL, et al. Annual report to the nation on the status of cancer, part 1: National cancer statistics. Cancer. 2022;128(24):4251–84.CrossRefPubMed
3.
go back to reference Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–9.CrossRefPubMed Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–9.CrossRefPubMed
4.
go back to reference Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.CrossRefPubMed Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.CrossRefPubMed
5.
go back to reference Paz-Ares L, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):198–211.CrossRefPubMed Paz-Ares L, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):198–211.CrossRefPubMed
6.
go back to reference Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.CrossRefPubMed Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.CrossRefPubMed
7.
go back to reference Bodor JN, Boumber Y, Borghaei H. Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer. 2020;126(2):260–70.CrossRefPubMed Bodor JN, Boumber Y, Borghaei H. Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer. 2020;126(2):260–70.CrossRefPubMed
8.
go back to reference Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.CrossRefPubMed Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.CrossRefPubMed
9.
go back to reference Lu T, Yang X, Huang Y, Zhao M, Li M, Ma K, et al. Trends in the incidence, treatment, and survival of patients with lung cancer in the last four decades. Cancer Manag Res. 2019;11:943–53.CrossRefPubMedPubMedCentral Lu T, Yang X, Huang Y, Zhao M, Li M, Ma K, et al. Trends in the incidence, treatment, and survival of patients with lung cancer in the last four decades. Cancer Manag Res. 2019;11:943–53.CrossRefPubMedPubMedCentral
10.
go back to reference Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.CrossRefPubMed Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.CrossRefPubMed
11.
go back to reference Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, et al. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol. 2022;40(12):1301–11.CrossRefPubMedPubMedCentral Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, et al. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol. 2022;40(12):1301–11.CrossRefPubMedPubMedCentral
12.••
go back to reference Felip E, Altorki N, Zhou C, Csoszi T, Vynnychenko I, Goloborodko O, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet 2021;398(10308):1344–1357. Phase III trial demonstrating a significant DFS benefit with adjuvant atezolizumab as compared to best supportive care in patients with resected stage II – IIIA, PD-L1 ≥ 1% NSCLC. Findings from this study led to the first FDA approval of a checkpoint inhibitor to be used in the adjuvant setting in NSCLC. This approval is just for NSCLC tumors with PD-L1 ≥ 1% expression. Felip E, Altorki N, Zhou C, Csoszi T, Vynnychenko I, Goloborodko O, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet 2021;398(10308):1344–1357. Phase III trial demonstrating a significant DFS benefit with adjuvant atezolizumab as compared to best supportive care in patients with resected stage II – IIIA, PD-L1 ≥ 1% NSCLC. Findings from this study led to the first FDA approval of a checkpoint inhibitor to be used in the adjuvant setting in NSCLC. This approval is just for NSCLC tumors with PD-L1 ≥ 1% expression.
15.••
go back to reference O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274–1286. Phase III trial demonstrating a significant DFS benefit with adjuvant pembrolizumab as compared to placebo in patients with resected stage IB – IIIA NSCLC. Findings from this study led to the FDA approval of pembrolizumab in the adjuvant setting in NSCLC, irrespective of tumor PD-L1 expression. O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274–1286. Phase III trial demonstrating a significant DFS benefit with adjuvant pembrolizumab as compared to placebo in patients with resected stage IB – IIIA NSCLC. Findings from this study led to the FDA approval of pembrolizumab in the adjuvant setting in NSCLC, irrespective of tumor PD-L1 expression.
16.
go back to reference Bodor JN, Bauman JR, Handorf EA, Ross EA, Clapper ML, Treat J. Real-world progression-free survival (rwPFS) and the impact of PD-L1 and smoking in driver-mutated non-small cell lung cancer (NSCLC) treated with immunotherapy. J Cancer Res Clin Oncol. 2023;149(5):1755–63.CrossRefPubMed Bodor JN, Bauman JR, Handorf EA, Ross EA, Clapper ML, Treat J. Real-world progression-free survival (rwPFS) and the impact of PD-L1 and smoking in driver-mutated non-small cell lung cancer (NSCLC) treated with immunotherapy. J Cancer Res Clin Oncol. 2023;149(5):1755–63.CrossRefPubMed
17.
go back to reference Gainor JF, Shaw AT, Sequist LV, Fu X, Azzoli CG, Piotrowska Z, et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin Cancer Res. 2016;22(18):4585–93.CrossRefPubMedPubMedCentral Gainor JF, Shaw AT, Sequist LV, Fu X, Azzoli CG, Piotrowska Z, et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis. Clin Cancer Res. 2016;22(18):4585–93.CrossRefPubMedPubMedCentral
18.
go back to reference Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, et al. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung cancer-a meta-analysis. J Thorac Oncol. 2017;12(2):403–7.CrossRefPubMed Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, et al. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung cancer-a meta-analysis. J Thorac Oncol. 2017;12(2):403–7.CrossRefPubMed
20.
go back to reference Hellmann MD, Chaft JE, William WN Jr, Rusch V, Pisters KM, Kalhor N, et al. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet Oncol. 2014;15(1):e42-50.CrossRefPubMedPubMedCentral Hellmann MD, Chaft JE, William WN Jr, Rusch V, Pisters KM, Kalhor N, et al. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet Oncol. 2014;15(1):e42-50.CrossRefPubMedPubMedCentral
21.
go back to reference Rusch VW, Nicholas A, Patterson GA, Waqar SN, Toloza EM, Haura EB, et al. Surgical results of the Lung Cancer Mutation Consortium 3 trial: a phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non-small cell lung cancer. J Thorac Cardiovasc Surg. 2022. Rusch VW, Nicholas A, Patterson GA, Waqar SN, Toloza EM, Haura EB, et al. Surgical results of the Lung Cancer Mutation Consortium 3 trial: a phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non-small cell lung cancer. J Thorac Cardiovasc Surg. 2022.
22.
go back to reference Cascone T, William WN Jr, Weissferdt A, Leung CH, Lin HY, Pataer A, et al. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med. 2021;27(3):504–14.CrossRefPubMedPubMedCentral Cascone T, William WN Jr, Weissferdt A, Leung CH, Lin HY, Pataer A, et al. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med. 2021;27(3):504–14.CrossRefPubMedPubMedCentral
23.
go back to reference Provencio M, Nadal E, Gonzalez-Larriba JL, Martinez-Marti A, Bernabe R, Bosch-Barrera J, et al. Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2023;389(6):504–13.CrossRefPubMed Provencio M, Nadal E, Gonzalez-Larriba JL, Martinez-Marti A, Bernabe R, Bosch-Barrera J, et al. Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2023;389(6):504–13.CrossRefPubMed
24.••
go back to reference Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973–1985. Phase III trial demonstrating a significant EFS and pCR benefit with neoadjuvant nivolumab plus platinum-based chemotherapy as compared to chemotherapy alone in patients with resectable stage IB to IIIA NSCLC. Findings from this study led to the first FDA approval of a checkpoint inhibitor plus chemotherapy regimen to be used in the neoadjuvant setting in NSCLC. Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973–1985. Phase III trial demonstrating a significant EFS and pCR benefit with neoadjuvant nivolumab plus platinum-based chemotherapy as compared to chemotherapy alone in patients with resectable stage IB to IIIA NSCLC. Findings from this study led to the first FDA approval of a checkpoint inhibitor plus chemotherapy regimen to be used in the neoadjuvant setting in NSCLC.
26.
go back to reference Girard N, Spicer J, Provencio M, Lu S, Wang C. et al. Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816. European Lung Cancer Congress 2023, Abstract 84O. Girard N, Spicer J, Provencio M, Lu S, Wang C. et al. Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816. European Lung Cancer Congress 2023, Abstract 84O.
27.
go back to reference Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, et al. AEGEAN: a phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14–19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT005. Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, et al. AEGEAN: a phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14–19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT005.
28.
go back to reference Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med. 2023;389(6):491–503.CrossRefPubMed Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med. 2023;389(6):491–503.CrossRefPubMed
30.
go back to reference Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321–8.CrossRefPubMedPubMedCentral Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321–8.CrossRefPubMedPubMedCentral
31.
go back to reference Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.CrossRefPubMedPubMedCentral Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–39.CrossRefPubMedPubMedCentral
32.
go back to reference Jiang Q, Xie M, He M, Yan F, Zhang X, Yu S. Anti-PD-1/PD-L1 antibodies versus docetaxel in patients with previously treated non-small-cell lung cancer. Oncotarget. 2018;9(7):7672–83.CrossRefPubMed Jiang Q, Xie M, He M, Yan F, Zhang X, Yu S. Anti-PD-1/PD-L1 antibodies versus docetaxel in patients with previously treated non-small-cell lung cancer. Oncotarget. 2018;9(7):7672–83.CrossRefPubMed
33.
go back to reference Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711–23.CrossRefPubMed Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711–23.CrossRefPubMed
34.
go back to reference Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohe C, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137–47.CrossRefPubMed Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohe C, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137–47.CrossRefPubMed
35.
go back to reference Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261–72.CrossRefPubMedPubMedCentral Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261–72.CrossRefPubMedPubMedCentral
36.
go back to reference Waldeck S, Mitschke J, Wiesemann S, Rassner M, Andrieux G, Deuter M, et al. Early assessment of circulating tumor DNA after curative-intent resection predicts tumor recurrence in early-stage and locally advanced non-small-cell lung cancer. Mol Oncol. 2022;16(2):527–37.CrossRefPubMed Waldeck S, Mitschke J, Wiesemann S, Rassner M, Andrieux G, Deuter M, et al. Early assessment of circulating tumor DNA after curative-intent resection predicts tumor recurrence in early-stage and locally advanced non-small-cell lung cancer. Mol Oncol. 2022;16(2):527–37.CrossRefPubMed
Metadata
Title
Perioperative Immunotherapy in Non-Small Cell Lung Cancer
Authors
Jenny O’Brien, MD, PhD
J. Nicholas Bodor, MD, PhD
Publication date
13-12-2023
Publisher
Springer US
Published in
Current Treatment Options in Oncology / Issue 12/2023
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-023-01160-6

Other articles of this Issue 12/2023

Current Treatment Options in Oncology 12/2023 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine